Williams Syndrome: Getting to the Heart of a Rare Genetic Disorder

St. Louis Children’s Hospital has been part of 19-year-old Tim Schmitt’s family since he was born with Williams syndrome—a genetic condition that affects nearly 30,000 people in the United States.

Washington University physician Beth Kozel, MD, PhD, feels very fortunate to work with children and adults like Tim who have Williams syndrome. Sociable and uninhibited, these kids aren’t afraid to approach strangers and strike up a conversation. "It's fun to be their doctor, because every child is such a delight," says Dr. Kozel, a genetics specialist at St. Louis Children’s Hospital and a Children’s Discovery Institute Faculty Scholar.

But there's a flip side. Williams syndrome can cause a range of problems, including developmental delays, narrowing of the blood vessels and heart failure, where the heart can’t adequately pump blood to the rest of the body. Only a small percentage of children with this rare genetic disorder will develop life-threatening vascular disease, but it's difficult to predict which ones will be affected. "We need to do a better job of giving parents an idea of which parts of the condition they need to worry about, and which ones are not relevant to the child, so they can focus their energy on the right things," Dr. Kozel says.

By combining animal models with human studies, Dr. Kozel is investigating genetic factors that influence the severity of vascular disease in patients with Williams syndrome. Through the Faculty Scholar Award given by the Children’s Discovery Institute, she has identified genes that regulate blood vessel narrowing and control disease severity in mice. "The Institute’s Faculty Scholar award will allow me to apply my experience in mouse genetics to human studies, which is new for me," Dr. Kozel says.

To translate the findings to patients, she is collaborating with the Williams Syndrome Association. By collecting DNA samples from these children, she hopes to identify biomarkers that would indicate the severity of vascular disease. Unlike the standard approach of using an echocardiogram, the new biomarkers would predict what will happen in the future rather than simply read out the current biological state of patients. "Our approach would help us to stratify patients into groups based on what type of monitoring they will need and determine which medications should be used to control blood vessel problems," Dr. Kozel says.

As for Tim, he is a shining example of the power of optimism. He underwent a kidney transplant at Children’s Hospital in 2008 and has since visited the hospital regularly for follow-up appointments. With a zest for life, and a love for music and the St. Louis Cardinals, Tim is grateful to his hospital family for helping him to thrive in a world where there are so many things to enjoy.

Williams syndrome (WS) is a rare genetic disorder that is associated with developmental delays and medical problems affecting multiple parts of the body. Williams syndrome occurs in about 1 in 8,000 births and features include:

Difficulty with potty training, increased frequency with which the child needs to go or urgency leading to accidents or the feeling of pain with urination

Hernias and other problems of connective tissue such as loose or tight joints or scoliosis

While there is no cure for Williams syndrome, many families benefit from the team approach at the Williams Syndrome Center at St. Louis Children’s Hospital where multiple doctors experienced in the condition collaborate to help a child’s health and development.